It is certain and established that overcrowding represents one of the main problems that has been affecting global health and the functioning of the healthcare system in the last decades, and this is especially true for the emergency department (ED). Since 1980, overcrowding has been identified as one of the main factors limiting correct, timely, and efficient hospital care. The more recent COVID-19 pandemic contributed to the accentuation of this phenomenon, which was already well known and of international interest. Considering what would appear to be a trivial definition of overcrowding, it may seem simple for the reader to hypothesize solutions for what seems to be one of the most avoidable problems affecting the hospital system. However, proposing solutions to overcrowding, as well as their implementation, cannot be separated from a correct and precise definition of the issue, which must consider the main causes and aggravating factors. In light of the need of finding solutions that can put an end to hospital overcrowding, this review aims, through a review of the literature, to summarize the triggering factors, as well as the possible solutions that can be proposed.

Background It is still unclear how to combine biomarkers to identify patients who will truly benefit from anti-PD-1 agents in NSCLC. This study investigates exosomal mRNA expression of PD-L1 and IFN-γ, PD-L1 polymorphisms, tumor mutational load (TML) in circulating cell-free DNA (cfDNA) and radiomic features as possible predictive markers of response to nivolumab and pembrolizumab in metastatic NSCLC patients. Methods Patients were enrolled and blood (12 ml) was collected at baseline before receiving anti-PD-1 therapy. Exosome-derived mRNA and cfDNA were extracted to analyse PD-L1 and IFN-γ expression and tumor mutational load (TML) by digital droplet PCR (ddPCR) and next-generation sequencing (NGS), respectively. The PD-L1 single nucleotide polymorphisms (SNPs) c.-14-368 T > C and c.*395G > C, were analysed on genomic DNA by Real-Time PCR. A radiomic analysis was performed on the QUIBIM Precision® V3.0 platform. Results Thirty-eight patients were enrolled. High baseline IFN-γ was independently associated with shorter median PFS (5.6 months vs. not reached p = 0.0057), and levels of PD-L1 showed an increase at 3 months vs. baseline in patients who progressed (p = 0.01). PD-L1 baseline levels showed significant direct and inverse relationships with radiomic features. Radiomic features also inversely correlated with PD-L1 expression in tumor tissue. In subjects receiving nivolumab, median PFS was shorter in carriers of c.*395GG vs. c.*395GC/CC genotype (2.3 months vs. not reached, p = 0.041). Lastly, responders had higher non-synonymous mutations and more links between co-occurring genetic somatic mutations and ARID1A alterations as well. Conclusions A combined multiparametric approach may provide a better understanding of the molecular determinants of response to immunotherapy.

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High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

Background: Stomatitis is highly prevalent in patients with cancer treated with the mammalian target of rapamycin inhibitor everolimus; it usually has an early onset and may compromise treatment dose intensity and patients’ quality of life. Within the randomized controlled Stomatitis Prevention trial (STOP, ISRCTN14568888), we investigated the possibility of using a commercial natural multicomponent mouthwash (Orasol Plus®) to prevent the development of stomatitis of any grade in patients with advanced renal cell carcinoma (RCC) treated with everolimus. Methods: Overall, 62 patients were randomized to receive either Orasol Plus in addition to oral hygiene or oral hygiene alone (31 patients per treatment arm). Results: In the whole study population, 28 episodes of stomatitis were observed (41.9%); in only 2 patients, stomatitis occurred more than once (2 episodes). As expected, the episodes of stomatitis occurred early in the course of treatment with everolimus. Treatment with Orasol Plus prevented the onset of everolimus-induced stomatitis: only 8 episodes of stomatitis were observed in the treated group with Orasol Plus in addition to oral hygiene vs 20 episodes in the group treated with oral hygiene only ( p = 0021). Also, a reduction in the average duration of mucositis in patients treated with Orasol Plus compared to patients treated with oral hygiene only was observed (8 days vs 11.2 days, p = 0.0416). Conclusion: This study showed that the use of a natural multicomponent mouthwash coupled with regular oral hygiene was able to reduce the severity and duration of everolimus-induced stomatitis in patients with RCC. Trial registration number: ISRCTN14568888